The objective is to investigate the ionic processes underlying cardiac excitation and contraction. The investigation focusses on the role of the intracellular concentrations of K and Na on cross-ionic interactions. The chosen preparation, frog ventricular muscle has been extensively investigated and the contractile process is well controlled by the clampable surface membrane due to a virtual lack of sarcoplasmic reticulum. The single sucrose gap voltage-clamp technique is used to control the membrane potential and to measure the membrane current and the isometric tension. The intracellular concentration of K will be monitored simultaneously by measuring the radioactive emission from the preparation when 42K is added to the perfusate. Additional information about the intracellular ionic concentrations will be obtained using 22Na or 24Na, K-selective microelectrodes and measurements of reversal potentials for components of the membrane current. The following interventions are known to decrease the intracellular K concentration and will be used to alter the intracellular ionic composition: low temperatures, low extracellular K concentrations, long depolarizing clamp pulses, rapid stimulation and acetyl strophantidin (digitalis). The investigation will attempt to answer the questions: Passive membrane currents: a) How are the membrane currents influenced by the intracellular ion cencentrations? b) Is the conductance of the resting membrane decreased when the intracellular K concentration is decreased? c) Is the threshold of excitation decreased under these conditions? d) Is the speed of propagation decreased? Active transport: e) Is the Na-K exchange pump electrogenic? f) What is the coupling ratio for Na and K? g) Does the activity of the pump alter the shape of the action potential? Excitation contraction coupling: h) How does the intracellular concentrations of K and Na influence the tension-voltage relations? i) To what extent is contraction controlled by a Na-Ca exchange mechanism? The answer to these questions will advance the development of a complete ionic hypothesis for the heart.